Introduction 1 2 3 4 5 8 9 12 13 14 15 Studying the determinants of patients’ perceived burden of upper GI endoscopy, e.g. by comparing data from different patient groups, may allow for the identification of patient groups who are likely to experience more pain or discomfort than others. This information can be used in practice guidelines, e.g. on provision of sedation to prevent pain and discomfort, or other types of patient support. Studying determinants of patients’ perceived burden is of additional interest from the perspective of evaluation research. If patients’ perception of the burden of endoscopy differs by the context of e.g., surveillance or diagnostic work-up, the generalisability of data from one context to another is limited. 16 Methods Ethics approval The Medical Ethical Review Board of Erasmus MC—University Medical Center Rotterdam, The Netherlands, approved of the study (MEC 03.1064; October 9, 2003). Patients 16 Patients with non-specific upper GI symptoms (NS) were referred for endoscopy by their respective GPs because of non-specific upper GI symptoms. They needed to be able to read the Dutch language, provide informed consent, not to have “alarm symptoms” such as hematemesis, melena, or dysphagia, and not be diagnosed with BE previously. plus Endoscopic procedure 17 Hypotheses 1 Table 1 Potential determinants of perceived burden of endoscopy for three patient groups Determinant BE NS CA  Indication for endoscopy Regular endoscopic surveillance for early detection of cancer To find out if symptoms can be explained by e.g. a hiatal hernia or duodenal ulcer; a life-threatening diagnosis is not expected. To determine whether intentionally curative therapy is possible or not Endoscopy experience Yes, under endoscopic surveillance  Limited, ranging from 0 to some  Yes (by definition: at least one previous endoscopy needed to diagnose the cancer) Generic health status Generally healthy  Mild impairment (aspecific gastrointestinal symptoms) Seriously impaired (cancer diagnosis) Age In-between Youngest Older Sex More males than females  Equal sex distribution Predominantly male Endoscopy procedure Normal endoscopy procedure, sedation only on patient request Normal endoscopy procedure, sedation only on patient request Endoscopy combined with ultrasonography; sedation routinely offered Questionnaires and measurements 16 Pain and discomfort  16 Symptoms  16 Psychological distress (BE and NS patients) 18 19 18 19 n 19 20 21 22 Psychological distress (CA patients) For CA patients we omitted the HAD and the IES measures regarding the endoscopy itself, because we expected that distress in these patients was already at the top of the scale, making any additional distress caused by the procedure itself indiscernible. The IES to assess specific distress regarding the endoscopy result was included in the questionnaire at the day of endoscopy, because these patients received the endoscopy results earlier than the next questionnaire. Demographics and other data 23 25 Analyses Differences in demographic and treatment characteristics between patient groups were analysed by Chi-square tests for categorical variables or one-way analysis of variance (ANOVA) for continuous variables. 16 16 26 27 patient group (BE, NS or CA). This variable combines the differences in the endoscopy procedure (with or without EUS, sedation) and the indication to undergo the endoscopy. For BE and NS patients, this analysis was refined by additional separate analysis of the effect of the number of previous endoscopies (continuous, truncated at ≥20). baseline generic health status (EQ 5D summary score). whether sedation was administrated or not. baseline HAD anxiety score (not available for the CA patients). 16 The continuous HAD and IES scores were compared over time in SAS version 8.2 with repeated-measures ANOVA, using ‘Proc Mixed’ with REML and a compound symmetry covariance structure. Models comprised main effects of time (the measurements), confounders, determinants and interactions between determinants and time. Proportional odds models were estimated with Splus 6.0. All other analyses were conducted in SPSS version 11.0.1. Results Patients and response 16 P 2 Table 2 a  BE NS CA b N Group 180 214 82 N.A. 476 Mean age 62 (12) 54 (16) 64 (10) <0.001 474 Sex 119 (66%) 101 (47%) 66 (80%) <0.001 476 Employment      Paid employment 59 (34%) 85 (44%) 25 (36%) <0.001 438 Retired 87 (50%) 65 (34%) 38 (54%)   Unpaid/unemployed 29 (17%) 43 (22%) 7 (10%)   Civil status  Married/ together 134 (77%) 137 (69%) 57 (80%) 0.034 444 Never married/ tog. 13 (7%) 26 (13%) 3 (4%) Divorced 10 (6%) 23 (12%) 4 (6%) Widowed 18 (10%)  12 (6%) 7 (10%) Education  Primary 35 (20%) 37 (19%) 16 (23%) 0.498 435 Secondary 95 (56%) 122 (63%) 43 (61%) Tertiary 40 (24%) 35 (18%) 12 (17%) Hospital  Academic center (1) 37 (21%) 0 82 (100%) N.A. 476 Regional hospital (3) 143 (79%) 214 (100%) 0 Sedation 43 (27%) 18 (9%) 56 (77%) <0.001 419 Endoscopy number First 1 (1%)  99 (59%) Unknown <0.001 338 Second 26 (15%) 38 (23%) Third or later 144 (84%) 30 (18%) EQ–5D summary score 0.85 (0.18) 0.73 (0.22) 0.77 (0.21) <0.001 433 N.A., Not assessed a 16 b  F 16 P P P 2 Pain and discomfort  3 5 Table 3 a Discomfort Not Quite Very n b Introducing the endoscope 141 (34%) 177 (42%) 99 (24%) 417 P      NS 42 (24%) 76 (43%) 58 (33%) 176     BE 64 (37%) 81 (47%) 27 (16%) 172     CA 35 (51%) 20 (29%) 14 (20%) 69 Undergoing endoscopy 166 (40%) 162 (39%) 89 (21%) 417 P =      NS 62 (35%) 63 (36%) 51 (29%) 176     BE 75 (44%) 72 (42%) 25 (15%) 172     CA 29 (42%) 27 (39%) 13 (19%) 69 Removing the endoscope 290 (70%) 90 (22%) 35 ( 8%) 415 P      NS 97 (55%) 52 (30%) 26 (15%) 175     BE 144 (84%) 24 (14%) 3 ( 2%) 171     CA 49 (71%) 14 (20%) 6 ( 9%) 69 Period immediately after 317 (78%) 71 (17%) 20 ( 5%) 408 P     NS 132 (77%) 29 (17%) 11 ( 6%) 172     BE 136 (81%) 29 (17%) 4 ( 2%) 169     CA 49 (73%) 13 (19%) 5 ( 8%) 67 Discomfort summary score  (range: 0–8) Mean (sd)     All 2.35 (2.10)   406 P      NS 2.92 (2.36)   171     BE 1.88 (1.69)   168     CA 2.07 (1.99)   67 a 16 b Table 4 a Pain Not Quite Very n b Introducing the endoscope 332 (80%) 68 (16%) 17 (4%) 417 P     NS 135 (77%) 29 (17%) 12 (7%) 176     BE 145 (85%) 24 (14%) 2 (1%) 171     CA 52 (74%) 15 (21%) 3 (4%) 70 Undergoing endoscopy 320 (77%) 77 (19%) 17 (4%) 414 P     NS 141 (81%) 23 (13%) 10 (6%) 174     BE 137 (81%) 28 (17%) 5 (3%) 170     CA 42 (60%) 26 (37%) 2 (3%) 70 Removing the endoscope 365 (88%) 39 (9%) 11 (3%) 415 P     NS 152 (87%) 16 (9%) 6 (3%) 174     BE 157 (92%) 11 (6%) 3 (2%) 171     CA 56 (80%) 12 (17%) 2 (3%) 70 P Period immediately after 350 (84%) 52 (13%) 15 (4%) 417     NS 147 (84%) 23 (13%) 6 (3%) 176     BE 145 (85%) 22 (13%) 4 (2%) 171     CA 58 (83%) 7 (10%) 5 (7%) 70 Pain summary score  (range: 0–8) Mean (sd)     All 0.86 (1.60)   413 P = 0.02     NS 0.91 (1.81)   173     BE 0.66 (1.35)   170     CA 1.20 (1.60)   70 a 16 b Table 5 a Overall burden Not Quite Very n b Endoscopy in general 137 (34%) 204 (51%) 58 (15%) 399 P = 0.007     NS 48 (30%) 82 (50%) 32 (20%) 162     BE 68 (41%) 87 (52%) 12 ( 7%) 167     CA 21 (30%) 35 (50%) 14 (20%) 70 Overall burden summary  score (range: 0–2) Mean (sd)     All 0.80 (0.67)   399 P     NS 0.90 (0.70)   162     BE 0.67 (0.61)   167     CA 0.90 (0.71)   70 a 16 b 6 P Table 6 Differences in discomfort summary score, pain summary score and overall burden score, pair wise between patient groups (after correction for age, sex and employment status as confounders); and effects of other determinants than patient group on these differences Determinant Discomfort score Pain score Overall burden a b P a b P a b P NS compared to BE (BE = reference group) Patient group: NS versus BE 1.69 1.15–2.47 < 0.01 1.09 0.70–1.71 0.70 1.64 1.05–2.55 0.03     + Number of previous endoscopies 1.49 0.98–2.27 0.06 1.19 0.73–1.94 0.50 1.56 0.96–2.53 0.07     + Baseline EQ–5D 1.51 1.02–2.23 0.04 0.83 0.53–1.32 0.44 1.49 0.96–2.33 0.08     + Baseline anxiety 1.63 1.12–2.39 0.01 1.04 0.66–1.64 0.86 1.59 1.02–2.49 0.04     + Sedation 1.42 0.96–2.09 0.08 1.08 0.68–1.72 0.73 1.40 0.88–2.22 0.15 c Patient group: CA versus BE 1.22 0.75–1.99 0.42 2.69 1.51–4.77 <0.01 2.37 1.38–4.07 <0.01     + Baseline EQ–5D 1.07 0.66–1.74 0.79 2.32 1.29–4.18 <0.01 2.10 1.21–3.66 <0.01     + Sedation 2.06 1.16–3.64 0.01 2.71 1.40–5.27 <0.01 3.10 1.68–5.74 <0.01 a b c P P 6 6 P P Symptoms P P Psychological distress 1 Fig. 1 Differences between BE and NS groups in Hospital Anxiety and Depression (HAD) scale scores for general distress before and after upper GI endoscopy (mean scores, no adjustment for confounders)  P P 19 P P P P P P P Discussion This study is the first to investigate determinants of patients’ perceived burden of upper GI endoscopy. Patients undergoing endoscopy for different reasons reported a different burden from the procedure. BE patients who underwent endoscopy as part of regular surveillance, reported the lowest discomfort, pain and overall burden, confirming our hypotheses in this respect. Patients with non-specific GI complaints reported more discomfort from the procedure, while those diagnosed with cancer experienced more pain and both groups reported more overall burden than patients under surveillance for BE. These differences remained significant after adjustment for confounders (age, sex, employment status). Differences in baseline anxiety scores or in baseline general health (EQ–5D) did not explain the differences in reported discomfort or pain. Differences in the number of previous endoscopies, and in whether sedation was provided during endoscopy or not, explained part of the differences in reported discomfort between NS and BE patients. Whether sedation was provided or not did not explain the differences in reported pain and overall burden between BE and CA patients. The study also confirms that that upper GI endoscopy is burdensome for all groups of patients: two-thirds of the total group of patients reported discomfort and overall burden from the procedure, and patients were distressed beforehand. These results may however underestimate the actual burden because this empirical study was limited to patients who actually underwent upper GI endoscopy, hence excluding patients who refrained from undergoing endoscopy because of past or anticipated adverse experiences. Another potential limitation of our study results from the differences in response rates between the groups. Differences between patient groups were also found for symptoms resulting from the endoscopy. Of all symptoms explored, only throat ache increased after upper GI endoscopy. CA patients reported a higher increase in throat ache than BE patients and NS patients. As upper GI endoscopy hardly caused any symptoms, we considered an investigation into determinants of these differences to be less interesting and therefore omitted those analyses. Furthermore, BE and NS patients differed in the levels of generic (HAD) and specific (IES) distress they reported. Specific distress (IES) was significantly higher in NS patients than in BE patients, both regarding the endoscopy itself and its result. General distress (HAD) also differed between groups: BE patients reported less depression across all measurements and the pattern of anxiety and depression across measurements was different. However, general distress is not necessarily related to the endoscopy. The persistent higher depression scores across different time points suggest that NS patients have more depressive symptoms in general but that this was not related to the endoscopy. The different pattern of anxiety levels before and after endoscopy, however, suggests that the patient groups also differed in endoscopy-related distress. The pattern corroborated the findings of the specific (IES) distress scores: NS patients were more distressed than BE patients before the endoscopy. The investigated determinants did not explain the differences between groups in specific distress or general distress pattern, except for the number of previous endoscopies explaining part of the difference in the depression scores. BE patients thus reported less distress and also less pain or discomfort than other patient groups. This was not caused by differences in patient characteristics (age, sex, employment status, baseline anxiety, baseline general health). There are several potential reasons why the reported burden differs. Firstly, BE patients are under regular surveillance and may get used to or adapt to the procedure decreasing its burden. As the number of previous endoscopies explained the lower distress, discomfort and overall burden reported in the BE group, we conclude that getting used, or adapting to endoscopy plays a role. Secondly, patients who perceive a greater benefit of the test may weigh its burden differently and consequently report less burden. BE patients potentially have more to gain from early discovery of adenocarcinoma than NS patients, who are usually referred for endoscopy to detect potential explanations for their symptoms, and also more than CA patients for whom endoscopy and ultrasonography are only part of the procedure to determine their treatment options and prognosis. As we did not measure perceived expected benefit of the endoscopy we are not able to determine whether this mechanism is part of the explanation. Thirdly, the endoscopic procedure was slightly different for the different patient groups. CA patients received sedation more often. Adjusting for this difference into the analysis did not explain the differences in pain and overall burden, whereas the difference in reported discomfort became significant after adjustment for sedation. These results suggest that differences in the proportions of patients receiving sedation during endoscopy did not explain the differences between the groups, and that sedation was provided to those patients who really needed it. The procedure for CA patients also differed; they underwent upper GI endoscopy combined with ultrasonography, and for the combined procedure an endoscope with a slightly larger diameter is used. Our data did not allow us to test separately whether this affected perceived pain and overall burden. Finally, most CA patients had esophageal carcinoma, and this disease may make passing the endoscope through the esophagus more difficult and therefore more painful. 16 19 The observation that patients under regular endoscopic surveillance may adapt to this invasive procedure should not result in an underestimation of the burden of regular endoscopic surveillance. The search for less invasive surveillance tests should continue, and frequency of surveillance should preferably be established by evidence-based individualized estimates of risk of progression.